Ulcerative colitis (UC), one of the typical inflammatory bowel diseases caused by dysregulated immunity, still requires novel therapeutic medicine with high efficacy and low toxicity. Hericium erinaceus has been widely used to treat different health problems especially gastrointestinal sickness in China for thousands of years. Here, we isolated, purified, and characterized a novel low weight polysaccharide (HEP10, Mw: 9.9 kDa) from the mycelia of H. erinaceus in submerged culture. We explored the therapeutic effect of HEP10 on UC and explored its underlying mechanisms. On one hand, HEP10 suppressed the production of TNF-α, IL-1β, IL-6, inducible iNOS, and COX-2 in LPS challenged murine macrophage RAW264.7 cells, as well as in colons from DSS-induced colitis mice. On the other hand, HEP10 treatment markedly suppressed the activation of NLRP3 inflammasome, NF-κB, AKT, and MAPK pathways. Moreover, HEP10 reversed DSS-induced alternation of the gut community composition and structure by significantly increasing Akkermansia muciniphila and also promoting functional shifts in gut microbiota. Structural equation modeling also highlighted that HEP10 can change widely through gut microbiota. In conclusion, HEP10 has a better prebiotic effect than the crude polysaccharides of H. erinaceus, which can be used as a novel dietary supplement and prebiotic to ameliorate colitis.

Juice fermented with lactic acid bacteria (LAB) has received attention due to its health benefits, such as antioxidant and anti-inflammatory. Previous research on LAB-fermented goji juice mainly focused on exploring the changes in the metabolite profile and antioxidant activity in vitro, whereas the liver protection properties of LAB-fermented goji juice in vivo are still unknown. This study aimed to investigate the effects of Lacticaseibacillus paracasei E10-fermented goji juice (E10F), Lactiplantibacillus plantarum M-fermented goji juice (MF), Lacticaseibacillus rhamnosus LGG-fermented goji juice (LGGF) on preventing acute alcoholic liver injury with physiology, gut microbial, and metabolic profiles in mice. Compared with goji juice, E10F, MF, and LGGF enhanced the protective effect against liver injury by reducing serum alanine transaminase (ALT) levels, improving the hepatic glutathione (GSH) antioxidant system, and attenuating inflammation by decreasing the levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β. Furthermore, E10F, MF, and LGGF increased intestinal integrity, restructured the gut microbiota including Bacteroides and Lactobacillus, and altered gut microbial metabolites including kyotorphin, indolelactic acid, and N-methylserotonin. Pretreatment of different LAB-fermented goji juice in mice showed significant differences in gut microbiota and metabolism. The correlation analysis demonstrated that the increase of Lactobacillus, indolelactic acid, and N-methylserotonin by E10F, MF, and LGGF was positively correlated with reduced inflammation and improved liver and gut function. Taken together, E10F, MF, and LGGF all have the potential to be converted into dietary interventions to combat acute alcoholic liver injury. It provided a reference for the study of the hepatoprotective effect of LAB-fermented goji juice.

Gastric precancerous lesions (GPL) represent a heterogeneous, multi-stage process that involves transition from a benign to a malignant state. To optimize prevention and intervention strategies, accurate methods must clearly distinguish between precancerous stages and predict progression risks at early stages. The metabolomic profiles of 188 GPL tissues and matched normal tissues were characterized using ultra-high-performance liquid chromatography-tandem mass spectrometry. Both multivariate and univariate statistical analyses were used to identify metabolomic features differentiating normal, atrophic, and intestinal metaplasia states in the stomach, followed by preliminary functional validation. From experiments conducted on two cohorts, we established a reliable clinical gastric tissue metabolomic map, which clearly distinguished between normal, atrophic, and intestinalized gastric tissues. We then identified metabolic biomarkers that differentiated various GPL stages. Furthermore, key metabolites were validated in in vitro studies. Relative acyl group and glycerophospholipid abundance was higher in normal gastric tissue when compared to GPL, whereas organic acids were more prevalent in precancerous tissues than in normal tissues. A combination of glycerophosphocholine, tiglylcarnitine, malate, sphingosine, and γ-glutamylglutamic acid may serve as powerful biomarkers to distinguish normal tissue from GPL. We used ultra-high-performance liquid chromatography with tandem mass spectrometry to effectively characterize metabolomic profiles in clinical gastric tissue samples. Key metabolites were identified and validated using targeted metabolomics. This study identified the metabolomic profiles of gastric tissues with atrophy and intestinal metaplasia of the gastric mucosa, uncovering and preliminarily validating key metabolites that may be used to assess high-risk populations and diagnose GPL, potentially advancing targeted gastric cancer prevention and treatment efforts.

Background/Objectives: High-fat-diet (HFD) consumption drives chronic liver injury via gut dysbiosis and metabolic disturban. Apple cider vinegar, rich in polyphenols and organic acids, shows potential in metabolic regulation. This study aimed to investigate whether apple cider vinegar powder (ACVP) alleviates HFD-induced liver injury by modulating the gut–liver axis. Methods: For 12 weeks, C57BL/6 J mice received daily ACVP gavage while being fed a HFD. A series of biological assessments were conducted, including systemic metabolic evaluations (body weight, serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST), and lipid/glucose levels), hepatic steatosis (hematoxylin and eosin (H&E) staining), intestinal microbiome characterization (16S rRNA gene genomic analysis), and comprehensive metabolite profiling of cecal contents (non-targeted metabolomics). Pearson correlation networks integrated multi-omics data. Results: ACVP attenuated HFD-induced weight gain by 26.3%, hepatomegaly and dyslipidemia, as well as reduced hepatic lipid vacuoles and serum ALT (48%)/AST (21.5%). ACVP restored gut microbiota diversity, enriching Muribaculaceae. Cecal metabolomics identified 38 HFD-perturbed metabolites reversed by ACVP, including indolelactate, hyocholate, and taurocholic acid. the Kyoto encyclopedia of genes and genomes (KEGG) analysis revealed ACVP-mediated recovery of linoleic acid metabolism. Correlation networks linked Akkermansia to anti-inflammatory metabolites (e.g., trans-ferulic), while Desulfobacterota correlated with pro-inflammatory oxylipins (e.g., 12,13-dihydroxy-9Z-octadecenoic acid (DHOME)). Conclusions: ACVP mitigates HFD-induced liver injury by remodeling gut microbiota, restoring microbial metabolites, and enhancing gut–liver crosstalk.

Desulfovibrio (DSV), sulfate-reducing gut bacteria that generate hydrogen sulfide (H₂S), can impact host health through diverse mechanisms including bile acid (BA) metabolism. Although intestinal overgrowth of DSV expands the BA pool and promotes liver injury, its causal role in hepatic pathophysiology remains incompletely defined. Here, by employing complementary interventions of cholic acid (CA) supplementation and the BA sequestrant cholestyramine in mouse models, we show that DSV-driven liver injury is mediated by aberrant BA metabolism coupled with gut microbial remodeling. CA alone induced overt hepatic damage, whereas supplemental DSV did not further exacerbate injury caused by excessive CA. Intervention with the BA sequestrant cholestyramine markedly attenuated DSV-elicited hepatic inflammatory and histological alterations, which were associated with an upregulation of the intestinal BAs pool. Hepatic expression of BAs synthetic genes Cyp7a1 and Cyp8b1 verified a negative-feedback regulation of BA metabolism upon treatments. 16S rRNA gene sequencing revealed that CA, DSV, and the cholestyramine all significantly influenced the gut microbiota. CA reduced microbial richness and drove community separation, while DSV intervention under high BA conditions enriched specific biomarkers including Eubacterium ventriosum and Enterorhabdus. Notably, the administration of cholestyramine attenuated these DSV-associated microbial shifts and further reduced overall species richness, confirming the integral role of BA dynamics in shaping the gut microbial community. Collectively, our research reveals the intricate link between DSV, BAs, and gut microbiota in liver injury, and suggests that modulation of BAs may hold therapeutic potential for DSV-associated liver hepatic conditions.

Cereal vinegar sediment (CVS), a byproduct of traditional vinegar fermentation, has been regarded as a health-promoting product. However, its role in genetically induced hyperlipidemia remains unclear. This study systematically evaluated the effects of Dade-CVS (DD-CVS) and Hengshun-CVS (HS-CVS) on apolipoprotein-E-deficient (Apoe^−/−) mice. Both CVS varieties significantly improve certain serological parameters of Apoe^−/− mice, although the overall impact on serum indicators remains limited. Nevertheless, 16S rRNA sequencing revealed that CVS treatment reshaped gut microbial communities to a notable extent. Compared with the Apoe^−/− mice, the DD-CVS treatment significantly increased the relative abundance of Dubosiella while reducing the genus Desulfovibrio, whereas the HS-CVS treatment inhibited the growth of Bifidobacterium and Akkermansia. The pathways predicted in the KO-DD group included vitamin, amino acid, and energy metabolism, while HS-CVS treatment was associated with bile acid biosynthesis and energy pathways. Metabolomic analysis showed that several key metabolites, including N1-acetylspermidine, succinic acid, and 25-hydroxycholesterol, were significantly altered following CVS supplementation. Correlation analysis revealed significant associations between serum indicators and these metabolites. Alistipes, Enterorhabdus, and Romboutsia were also correlated with serum indicators. Overall, these findings indicate that CVS primarily modulated the gut microbiota–metabolite axis and partial lipid modulation in hyperlipidemic mice. The study provides a reference for studies on the beneficial functions of CVS in hyperlipidemia.